Project Summary Nanoparticles are moving towards use as consumer products and therapeutic agents, and are gaining prevalence as environmental toxins. There is increasing concern on the impact that nanoparticles have on human health, specifically the lung. The lung is the most susceptible region of the body to interact with environmental particulates. Current studies of nanoparticle interaction with cells lacks insight on the mechanisms that results in inflammation and cell death. Nanoparticle exposure in static monocultures may not predict the complex biochemical responses triggered in the human lung. Expensive, ethically challenged animal models, lack the capability for mechanistic studies. Whereas, lung-on-a-chip microfluidic platforms offer increasingly sophisticated methods to study the in vivo lung response. These platforms do so by applying hydrodynamic and mechanical forces to cocultures of endothelial and differentiated epithelial cells to mimic the physiological environment within the alveolar-capillary interface. There is an increasing need to use these dynamic platforms to study the interaction of nanoparticles on lung tissue. To this end, my fabricated lung-on-a-chip platform enables monitoring intercellular fluid leakage and live cell imaging in response to induced inflammation. With these tools, the project seeks to use dynamic imaging to study the impact of aerosolized nanoparticles on lung tissue. The tissue will be monitored for the progression of inflammation and nanoparticle migration.